Figure from:Basic Fibroblast Growth Factor Increases Long-Term Survival of Spinal Motor Neurons and Improves Respiratory Function after Experimental Spinal Cord Injury

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Figure 2. Effects of incomplete contusive SCI at T8 on respiratory function at 24 hr after injury. a, Plethysmograph tracings of respiratory flow rate (units, ml/sec) obtained from conscious rats breathing room ait 24 hr after laminectomy alone (top) or laminectomy and SCI (bottom). b, Comparison of average tidal volume (/eft) and f (right) before (Pre) and 24 hr after (Post) surgery for groups of rats subjected to laminectomy alone or SCI (10 gm X 2.5 cm weight drop) at T8 (n = 3 per group). Asterisks indicate a significant difference relative to presurgery values (unpaired ¢ test, p < 0.05). — Figure 2 Effects of incomplete contusive SCI at T8 on respiratory function at 24 hr after injury. a, Plethysmograph tracings of respiratory flow rate (units, ml/sec) obtained from conscious rats breathing room ait 24 hr after laminectomy alone (top) or laminectomy and SCI (bottom). b, Comparison of average tidal volume (/eft) and f (right) before (Pre) and 24 hr after (Post) surgery for groups of rats subjected to laminectomy alone or SCI (10 gm X 2.5 cm weight drop) at T8 (n = 3 per group). Asterisks indicate a significant difference relative to presurgery values (unpaired ¢ test, p < 0.05).

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Figure 3. Effects of SCI and FGF2 treatment on respiratory parameters repeatedly measured over 5 weeks after SCI. Vertical bars represent the average Ve (a), Vt (b), and f (c) for groups that were subjected to SCI (10 gm X 2.5 cm weight drop) and then received either VEH alone (open bars; n = 8 until day 30 p.i.; n = 7 at day 35 p.i.) or 3 wg of FGF2 (solid bars; n = 8). a, There was no significant effect of SCI or treatment with FGF2 on Ve. b, Vt was significantly reduced in the VEH-treated group at 24 hr and 7 d p.i. compared with that in the preinjury group or the FGF2-treated group evaluated at the same time after injury. c, f was significantly higher in the VEH-treated group at 24 hr and 7 d pii. compared with that in the preinjury group or the FGF2-treated group evaluated at the same time after injury. Symbols indicate a significant (*p < 0.05) difference from preinjury values and a significant difference between VEH- and FGF2-treated groups at the same time (*two-way repeated measures ANOVA followed by Tukey’s procedure).

Figure 4. Effects of SCI and FGF2 treatment on the respiratory response to breathing air mixtures containing 5 or 7% CO, at 24 hr and 7 d after SCI. Vertical bars represent the average Ve, Vt, and f while breathing 5 or 7% CO, for the VEH- and FGF2-treated groups of rats whose baseline respiratory parameters are shown in Figure 3. Symbols indicate significant (*p < 0.05) differences from values at 24 hr before SCI and a significant difference between VEH- and FGF2-treated groups at the same time after SCI (*two-way repeated measures ANOVA followed by Tukey’s procedure).

Figure 6. Absence of effect of FGF2 treatment on hindlimb function over time after SCI. Symbols represent the average (+ SEM) behavioral scores for groups that received VEH alone (O; n = 8 until day 30 p.i.;n = 7 at day 35 p.i.) or 3 wg of FGF2 (@; n = 8). Where no error bar is shown, the SEM was smaller than the symbol. a, Overall hindlimb deficits ex- pressed as a CBS (Gale et al., 1985) that ranges from 100 in completely paralyzed rats to 0 in normal rats. b, Hindlimb locomotor function graded on an expanded scale [BBB (Basso et al., 1995)] that ranges from 0 in rats with complete hindlimb paralysis to 21 in normal rats. Analysis with repeated measures ANOVA showed no significant effect of FGF2 treat- ment on either the CBS or BBB. Figure 5. Effect of CO, concentration on minute ventilation before and at 24 hr after SCI. Symbols represent the average (+ SEM; n = 8) minute ventilation for the VEH-treated group at 24 hr before (L]) and 24 hr after SCI (©) and the FGF2-treated group at 24 hr before (A) and 24 hr after SCI (¥) when breathing air containing 0.04% (room air), 5%, or 7% CO). Linear regression lines are presented for each group and time point. There was a significant correlation between Ve and CO, concentrations before SCI for the groups of rats that were later injured and treated with VEH (r? = 0.9455) or FGF2 (r? = 0.9213). A strong and significant correlation was also seen at 24 hr after SCI for both the VEH-treated group (r? = 0.9619) and the FGF2-treated group (r? = 0.91645). However, the average slope of the regression lines was significantly different at 24 hr in the VEH-treated group compared with that in the preinjury group and the FGF2-treated group either before or at 24 hr after SCI (p < 0.001, Kruskal-Wallis ANOVA on ranks, followed by the Student-Newman- Keuls method, p < 0.05).

Figure 7. Residual spinal cord white matter at the lesion epicenters 5 weeks after injury. Tracings of sections through the lesion epicenters in rats of the VEH-treated group (a; n = 7) and FGF2-treated group (6; n = 8) show a similar incomplete thin rim of peripheral hypomyelinated white matter. The centers of the lesions (open area in the center of each section) contain cavities and a loose network of lesion cells (data not shown). Scale bar, 1 mm.

Figure 8. Neuroprotective effects of FGF2 treatment for VH and IML neurons evaluated at 5 weeks after SCI. a, b, Images of ChAT-positive VH neurons (a) and IML neurons (b) 4 mm caudal to the injury epicenter from a FGF2-treated rat. c, Effect of FGF2 treatment on the longitudinal depletion of spinal VH and IML neurons, as evaluated in luxol blue/hematoxylin-stained sections. Asterisks indicate significant differences between the FGF2-treated (n = 8) and VEH-treated (n = 7) groups (unpaired ¢ tests, p < 0.05). d, Effects of FGF2 treatment on sparing ChAT-positive VH motor neurons. Vertical bars indicate the mean (+ SEM) number of neurons per tissue section for the VEH-treated (open bars; n = 7) and FGF2-treated (solid bars; n = 8) rats at 3 and 4 mm rostral and caudal to the injury epicenters, as well as from equivalent sections of tissue from normal, uninjured rats (cross-hatched bars; n = 3). Two-way repeated measures ANOVA showed an overall significant effect of FGF2 treatment (p < 0.001). Asterisks indicate a significant difference in individual comparisons of the VEH- and FGF2-treated groups at each location (unpaired f tests, p < 0.05). e, Effect of FGF2 on the numbers of ChAT-positive IML neurons at 3 and 4 mm rostral and caudal to the injury epicenters. The FGF2-treated group showed an overall significantly larger number of ChAT-immunoreactive IML neurons (two-way repeated measures ANOVA, p < 0.001) and significant differences in individual comparisons of VEH- and FGF2-treated groups at the specified location (asterisk; unpaired ¢ test, p < 0.05)

Figure 9. Effect of FGF2 treatment on IML neurons retrogradely labeled by Fluoro-Gold placed in the adrenal medulla. a, Cluster of Fluoro-Gold- labeled IML neurons at 4 mm rostral to the epicenter in an FGF2-treated rat at 5 weeks after SCL. b, Reduced numbers of labeled IML neurons at ¢ mm rostral to the epicenter in a VEH-treated animal. Scale bar, 20 um. c, Quantitative analysis demonstrating that compared with the VEH-treatec group (open vertical bars; n = 7), the FGF2-treated group (solid vertical bars; n = 8) had significantly higher numbers of Fluoro-Gold-labeled IMI neurons at 4 mm rostral and caudal to the injury epicenters. At 7 mm rostral to the epicenter, no difference was observed between the two groups Asterisks indicate that means are significantly different from those of the VEH-treated group (p < 0.05, two-way repeated measures ANOVA followec by Tukey’s procedure).